Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.

IFCC interim guidelines on rapid point-of-care antigen testing for SARS-CoV-2 detection in asymptomatic and symptomatic individuals.

With an almost unremittent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections all around the world, there is a compelling need to introduce rapid, reliable, and high-throughput testing to allow appropriate clinical management and/or timely isolation of infected individuals. Although nucleic acid amplification testing (NAAT) remains the gold standard for detecting and theoretically quantifying SARS-CoV-2 mRNA in various specimen types, antigen assays may be considered a suitable alternative, under specific circumstances. Rapid antigen tests are meant to detect viral antigen proteins in biological specimens (e.g. nasal, nasopharyngeal, saliva), to indicate current SARS-CoV-2 infection. The available assay methodology includes rapid chromatographic immunoassays, used at the point-of-care, which carries some advantages and drawbacks compared to more conventional, instrumentation-based, laboratory immunoassays. Therefore, this document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 aims to summarize available data on the performance of currently available SARS-CoV-2 antigen rapid detection tests (Ag-RDTs), providing interim guidance on clinical indications and target populations, assay selection, and evaluation, test interpretation and limitations, as well as on pre-analytical considerations. This document is hence mainly aimed to assist laboratory and regulated health professionals in selecting, validating, and implementing regulatory approved Ag-RDTs.

Head-to-head evaluation on diagnostic accuracies of six SARS-CoV-2 serological assays.

In this study, we evaluated and compared six SARS-CoV-2 serology kits including the Abbott SARS-CoV-2 IgG assay, Beckman Access SARS-CoV-2 IgG assay, OCD Vitros OCD Anti-SARS-CoV-2 Total antibody assay, Roche Elecsys Anti SARS-CoV-2 assay, Siemens SARS-CoV-2 Total assay, and cPass surrogate viral neutralising antibody assay. A total of 336 non-duplicated residual serum samples that were obtained from COVID-19 confirmed patients (n=173) on PCR and negative controls (n=163) obtained pre-December 2019 before the COVID-19 pandemic were used for the study. These were concurrently analysed on the different immunoassay platforms and correlated with clinical characteristics. Our results showed all assays had specificity ranging from 99.3% to 100.0%. Overall sensitivity across all days of symptoms, in descending order were OCD (49.1%, 95% CI 41.8-56.5%), cPass (44.8%, 95% CI 37.5-52.3%), Roche (41.6%, 95% CI 34.5-49.0%), Siemens (39.9%, 95% CI 32.9-47.3%), Abbott (39.8%, 95% CI 32.9-47.3%) and Beckman (39.6%, 95% CI 32.5-47.3%). Testing after at least 14 days from symptom onset is required to achieve AUCs greater than 0.80. OCD and cPass performed the best in terms of sensitivity for >21 days symptoms with 93.3% (95% CI, 73.5-99.2%) and 96.7% (95% CI, 82.8-99.9%), respectively. Both also shared the greatest concordance, kappa 0.963 (95% CI 0.885-1.0), p<0.001, and had the lowest false negative rates. Serology results should be interpreted with caution in certain cases. False negatives were observed in a small number of individuals with COVID-19 on immunosuppressive therapy, pauci-symptomatic or who received antiretroviral therapy. In conclusion, all assays exhibited excellent specificity and total antibody assays with spike protein configurations generally outperformed nucleocapsid configurations and IgG assays in terms of diagnostic sensitivity.

The Risk of Spread of Infection During Craniotomy/Craniostomy on Patients with Active Coronavirus Disease 2019 (COVID-19) Infection: Myth or Fact?

OBJECTIVES: Craniotomies/craniostomies have been categorized as aerosol-generating procedures and are presumed to spread coronavirus disease 2019 (COVID-19). However, the presence of severe acute respiratory distress syndrome coronavirus 2 virus in the generated bone dust has never been proved. Our objective is to evaluate the presence of virus in the bone dust (aerosol) generated during emergency neurosurgical procedures performed on patients with active COVID-19. This would determine the true risk of disease transmission during the surgery. METHODS: Ten patients with active COVID-19 infection admitted to our institute in 1 month required emergency craniotomy/craniostomy. The bone dust and mucosal scrapings form paranasal sinuses (if opened) collected during these procedures were tested for the virus using reverse transcription polymerase chain reaction. The entire surgical team was observed for any symptoms related to COVID-19 for 14 days following surgery. RESULTS: Nine patients had moderate viral load in their nasopharyngeal cavity, as detected on reverse transcription polymerase chain reaction. None of the samples of bone dust from these 10 patients tested positive. Mucosal scrapping obtained in 1 patient in which mastoid air cells were inadvertently opened tested negative as well. No health workers from the operating room developed COVID-19-related symptoms. CONCLUSIONS: The bone dust generated during craniotomy/stomy of active patients does not contain the virus. The procedure on an active patient is unlikely to spread the disease. However, a study with larger cohort would be confirmatory.

Comparative Clinical Evaluation of the Roche Elecsys and Abbott Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Serology Assays for Coronavirus Disease 2019 (COVID-19).

CONTEXT.­: The use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic tests detects antibodies in the host, contributing to the identification of individuals who have been exposed to coronavirus disease 2019 (COVID-19). OBJECTIVE.­: To critically evaluate 2 commercially available SARS-CoV-2 serology tests. DESIGN.­: A total of 333 unique, nonduplicated serum samples obtained from COVID-19 patients (n = 170) and negative controls (n = 163) obtained before December 2019 were used in the study. Samples were tested on the Roche E411 and Abbott Architect i4000SR platforms, and results were correlated to reverse transcription polymerase chain reaction (PCR) results and clinical symptoms. RESULTS.­: There was a strong level of agreement in the qualitative results between both assays, with a Cohen κ value of .840, P < .001. The specificity for both Roche and Abbott were excellent at 100%. Roche exhibited marginally better performance in the 21 days or more group with a sensitivity of 90.6% (95% CI, 75.8%-96.8%) versus an Abbott sensitivity of 84.4% (95% CI, 68.3%-93.1%), as well as in the 14- to 20-day group with a sensitivity of 85.7% (95% CI, 65.4%-95.0%) versus an Abbott sensitivity of 81.0% (95% CI, 60.0%-92.3%). Less than 14 days of symptoms groups exhibited poor sensitivity at less than 50% for both assays. The areas under curve (± standard error) for Roche (0.894 ± 0.025, P < .001) and Abbott (0.884 ± 0.026, P < .001) were very similar. Potential confounders for negative serologic results include antiretroviral medication use and pauci-symptomatic patients. CONCLUSIONS.­: Specificities for high-throughput Roche and Abbott immunoassays are excellent, but users need to be cautious to interpret serologic test results after 14 days of symptoms to avoid false negatives.

SARS-CoV-2 in migrant worker dormitories: Geospatial epidemiology supporting outbreak management.

BACKGROUND: Migrant worker dormitories-residential complexes where 10-24 workers share living spaces-account for the majority of cases of SARS-CoV-2 infection in Singapore. To prevent overspill of transmission to the wider population, starting in early April 2020, residents were confined to their dormitories while measures were put in place to arrest the spread of infection. This descriptive study presents epidemiological data for a population of more than 60 000 migrant workers living in two barracks-style and four apartment-style dormitories located in western Singapore from April 3 to June 10, 2020. METHODS: Our report draws from data obtained over the first 50 days of outbreak management in order to describe SARS-CoV-2 transmission in high-density housing environments. Cumulative counts of SARS-CoV-2 cases and numbers of housing units affected were analyzed to report the harmonic means of harmonic means of doubling times and their 95% confidence intervals (CI). RESULTS: Multiple transmission peaks were identified involving at least 5467 cases of SARS-CoV-2 infection across six dormitories. Our geospatial heat maps gave an early indication of outbreak severity in affected buildings. We found that the number of cases of SARS-CoV-2 infection doubled every 1.56 days (95% CI 1.29-1.96) in barracks-style buildings. The corresponding doubling time for apartment-style buildings was 2.65 days (95% CI 2.01-3.87). CONCLUSIONS: Geospatial epidemiology was useful in shaping outbreak management strategies in dormitories. Our results indicate that building design plays an integral role in transmission and should be considered in the prevention of future outbreaks.

Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence.

The global coronavirus disease 2019 (COVID-19) has presented major challenges for clinical laboratories, from initial diagnosis to patient monitoring and treatment. Initial response to this pandemic involved the development, production, and distribution of diagnostic molecular assays at an unprecedented rate, leading to minimal validation requirements and concerns regarding their diagnostic accuracy in clinical settings. In addition to molecular testing, serological assays to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now becoming available from numerous diagnostic manufacturers. In both cases, the lack of peer-reviewed data and regulatory oversight, combined with general misconceptions regarding their appropriate use, have highlighted the importance of laboratory professionals in robustly validating and evaluating these assays for appropriate clinical use. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 has been established to synthesize up-to-date information on the epidemiology, pathogenesis, and laboratory diagnosis and monitoring of COVID-19, as well as to develop practical recommendations on the use of molecular, serological, and biochemical tests in disease diagnosis and management. This review summarizes the latest evidence and status of molecular, serological, and biochemical testing in COVID-19 and highlights some key considerations for clinical laboratories operating to support the global fight against this ongoing pandemic. Confidently this consolidated information provides a useful resource to laboratories and a reminder of the laboratory's critical role as the world battles this unprecedented crisis.

Biosafety measures for preventing infection from COVID-19 in clinical laboratories: IFCC Taskforce Recommendations.

Coronavirus disease 2019 (COVID-19) is the third coronavirus outbreak that has emerged in the past 20 years, after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). One important aspect, highlighted by many global health organizations, is that this novel coronavirus outbreak may be especially hazardous to healthcare personnel, including laboratory professionals. Therefore, the aim of this document, prepared by the COVID-19 taskforce of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), is to provide a set of recommendations, adapted from official documents of international and national health agencies, on biosafety measures for routine clinical chemistry laboratories that operate at biosafety levels 1 (BSL-1; work with agents posing minimal threat to laboratory workers) and 2 (BSL-2; work with agents associated with human disease which pose moderate hazard). We believe that the interim measures proposed in this document for best practice will help minimazing the risk of developing COVID-19 while working in clinical laboratories.

Harnessing the power of social media to support medical training during COVID-19.

Twitter offers a powerful means to share information, suggest ways to help and highlight useful initiatives during the global COVID-19 pandemic. We describe one successful Twitter campaign focusing on the role of medical students (#MedStudentCovid), led by the volunteer organisation Becoming A Doctor with support from leaders at the General Medical Council, Health Education England, NHS England and the World Health Organization.

IFCC Interim Guidelines on Biochemical/Hematological Monitoring of COVID-19 Patients.

Routine biochemical and hematological tests have been reported to be useful in the stratification and prognostication of pediatric and adult patients with diagnosed coronavirus disease (COVID-19), correlating with poor outcomes such as the need for mechanical ventilation or intensive care, progression to multisystem organ failure, and/or death. While these tests are already well established in most clinical laboratories, there is still debate regarding their clinical value in the management of COVID-19, particularly in pediatrics, as well as the value of composite clinical risk scores in COVID-19 prognostication. This document by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 provides interim guidance on: (A) clinical indications for testing, (B) recommendations for test selection and interpretation, (C) considerations in test interpretation, and (D) current limitations of biochemical/hematological monitoring of COVID-19 patients. These evidence-based recommendations will provide practical guidance to clinical laboratories worldwide, underscoring the contribution of biochemical and hematological testing to our collective pandemic response.

IFCC Interim Guidelines on Serological Testing of Antibodies against SARS-CoV-2.

Serological testing for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as an important component of the clinical management of patients with coronavirus disease 2019 (COVID-19) as well as the epidemiological assessment of SARS-CoV-2 exposure worldwide. In addition to molecular testing for the detection of SARS-CoV-2 infection, clinical laboratories have also needed to increase testing capacity to include serological evaluation of patients with suspected or known COVID-19. While regulatory approved serological immunoassays are now widely available from diagnostic manufacturers globally, there is significant debate regarding the clinical utility of these tests, as well as their clinical and analytical performance requirements prior to application. This document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 provides interim guidance on: (A) clinical indications and target populations, (B) assay selection, (C) assay evaluation, and (D) test interpretation and limitations for serological testing of antibodies against SARS-CoV-2 infection. These evidence-based recommendations will provide practical guidance to clinical laboratories in the selection, verification, and implementation of serological assays and are of the utmost importance as we expand our pandemic response from initial case tracing and containment to mitigation strategies to minimize resurgence and further morbidity and mortality.

IFCC Interim Guidelines on Molecular Testing of SARS-CoV-2 Infection.

The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection globally has relied extensively on molecular testing, contributing vitally to case identification, isolation, contact tracing, and rationalization of infection control measures during the coronavirus disease 2019 (COVID-19) pandemic. Clinical laboratories have thus needed to verify newly developed molecular tests and increase testing capacity at an unprecedented rate. As the COVID-19 pandemic continues to pose a global health threat, laboratories continue to encounter challenges in the selection, verification, and interpretation of these tests. This document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 provides interim guidance on: (A) clinical indications and target populations, (B) assay selection, (C) assay verification, and (D) test interpretation and limitations for molecular testing of SARS-CoV-2 infection. These evidence-based recommendations will provide practical guidance to clinical laboratories worldwide and highlight the continued importance of laboratory medicine in our collective pandemic response.

Operational considerations and challenges of biochemistry laboratories during the COVID-19 outbreak: an IFCC global survey.

Objectives: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 conducted a global survey to understand how biochemistry laboratories manage the operational challenges during the coronavirus disease 2019 (COVID-19) pandemic. Materials and methods: An electronic survey was distributed globally to record the operational considerations to mitigate biosafety risks in the laboratory. Additionally, the laboratories were asked to indicate the operational challenges they faced. Results: A total of 1210 valid submissions were included in this analysis. Most of the survey participants worked in hospital laboratories. Around 15% of laboratories restricted certain tests on patients with clinically suspected or confirmed COVID-19 over biosafety concerns. Just over 10% of the laboratories had to restrict their test menu or services due to resource constraints. Approximately a third of laboratories performed temperature monitoring, while two thirds of laboratories increased the frequency of disinfection. Just less than 50% of the laboratories split their teams. The greatest reported challenge faced by laboratories during the COVID-19 pandemic is securing sufficient supplies of personal protective equipment (PPE), analytical equipment, including those used at the point of care, as well as reagents, consumables and other laboratory materials. This was followed by having inadequate staff, managing their morale, anxiety and deployment. Conclusions: The restriction of tests and services may have undesirable clinical consequences as clinicians are deprived of important information to deliver appropriate care to their patients. Staff rostering and biosafety concerns require longer-term solutions as they are crucial for the continued operation of the laboratory during what may well be a prolonged pandemic.

Laboratory practices to mitigate biohazard risks during the COVID-19 outbreak: an IFCC global survey.

Objectives: A global survey was conducted by the IFCC Task Force on COVID-19 to better understand how general biochemistry laboratories manage the pre-analytical, analytical and post-analytical processes to mitigate biohazard risks during the coronavirus disease 2019 (COVID-19) pandemic. Methods: An electronic survey was developed to record the general characteristics of the laboratory, as well as the pre-analytical, analytical, post-analytical and operational practices of biochemistry laboratories that are managing clinical samples of patients with COVID-19. Results: A total of 1210 submissions were included in the analysis. The majority of responses came from hospital central/core laboratories that serve hospital patient groups and handle moderate daily sample volumes. There has been a decrease in the use of pneumatic tube transport, increase in hand delivery and increase in number of layers of plastic bags for samples of patients with clinically suspected or confirmed COVID-19. Surgical face masks and gloves are the most commonly used personal protective equipment (PPE). Just >50% of the laboratories did not perform an additional decontamination step on the instrument after analysis of samples from patients with clinically suspected or confirmed COVID-19. A fifth of laboratories disallowed add-on testing on these samples. Less than a quarter of laboratories autoclaved their samples prior to disposal. Conclusions: The survey responses showed wide variation in pre-analytical, analytical and post-analytical practices in terms of PPE adoption and biosafety processes. It is likely that many of the suboptimal biosafety practices are related to practical local factors, such as limited PPE availability and lack of automated instrumentation.